UMLS:C0023890 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An ELISA has been developed for detection of auto-antibodies against calmodulin. There was a significantly increased frequency (63.1%) of autoantibodies against calmodulin in 103 patients with chronic liver diseases as compared to that (30%) of patients with systemic lupus erythematosus and to that (6.9%) of normal subjects (p less than 0.01). IgG autoantibodies against calmodulin were detected in the patients with acute hepatitis (37.9%), chronic liver disease (45.6%) and also in the patients with systemic lupus erythematosus (30%). IgM autoantibodies against calmodulin were frequently found in patients with liver cirrhosis (52.2%), primary biliary cirrhosis (50%) and autoimmune chronic active hepatitis (38.7%), but rarely in patients with acute hepatitis (13.8%), chronic persistent hepatitis (9.5%) and systemic lupus erythematosus (0%). IgA autoantibodies against calmodulin were frequently found in liver cirrhosis (33.3%), primary biliary cirrhosis (42.9%) and autoimmune chronic active hepatitis (53.6%), but rarely in chronic persistent hepatitis (15.8%), chronic active hepatitis (14.3%) and systemic lupus erythematosus (0%). The occurrences of autoantibodies against calmodulin correlated neither with those of antismooth muscle antibody, antinuclear antibody and antimitochondrial antibody, nor with serum IgG concentrations. Autoantibodies against calmodulin did not cross-react with troponin, myosin light chain, calf thymus DNA and actin. The titer of autoantibodies against calmodulin was decreased by absorption of serum with calmodulin and the liver plasma membrane fraction. The immunoblotting experiment revealed the binding of autoantibodies against calmodulin to calmodulin. IgG fraction from a patient with autoimmune chronic active hepatitis inhibited the activation of phosphodiesterase by calmodulin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anticalmodulin autoantibody in liver diseases: a new antibody against a cytoskeleton-related protein. 355 8

Five Tupaia herpesviruses have been isolated until now: four in our laboratory which were termed THV-2, 3, 4, and 5, whereas THV-1 has been isolated by Melnick and his colleagues. THV-2 was isolated from tumour cell culture of a high-grade malignant lymphoma of a Tupaia, THV-3 was released from a cell culture of another Tupaia lymphoma, THV-4 from a spleen tissue culture of a moribund animal with finely granulated liver cirrhosis, and THV-5 from cultured spleen cells of an apparently healthy tree shrew. THV-1 to 5 were efficiently propagated, plaque-purified and cloned on Tupaia embryonic fibroblasts. The five isolates of Tupaia herpesviruses are easily distinguished from each other by restriction enzyme analysis of their genomes. THV-1 to 4 are highly pathogenic (lethality 100%) for juvenile Tupaias by intravenous inoculation. In contrast, only 25% lethality was found by intraperitoneal administration. THV-1 to 4 can persist as a latent infection in spleens of Tupaias and rabbits, which allows the recovery of infectious virus from cultured spleens of both animals. THV-2 and 3 induced hyperplasia of the thymus of rabbits which developed malignant thymoma in a few cases. The biological properties and genomic size and structure indicate that THV cannot be considered to belong to one of the three existing subfamilies of herpesviruses.
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PMID:Tree shrew (Tupaia) herpesviruses. 716 1

1. Dialkyltin compounds have been widely used in industry and agriculture, mainly as biocides, catalysts and plast stabilizer. In dependence on the length of the alkyl chains these organotins exert toxic effects on the immune system, the bile duct, liver and pancreas. It has been supposed that similar to organoarsenic the toxicity of the dialkyltin compounds is related to reactions with biological dithiol groups. Therefore, in the present study, the antidotal effects of 2,3-dimercapto-propane-1-sulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) on the organotoxic effects of dibutyltin dichloride (DBTC, single administration of 27 micromol kg(-1) b.w. i.v.) in rats were studied using different doses (100 and 500 micromol kg(-1) b.w.) and routes of administration (i.p. and p.o.) of both chelators. Several parameters of organotoxicity (thymus weight and cellularity, bile duct diameter, histological lesions of pancreas and liver, activities of amylase, lipase and alkaline phosphatase, bilirubin and hyaluronic acid in serum) were measured from 6 h to 8 weeks. 2. DMPS and DMSA diminished the DBTC induced bile duct, pancreas and liver lesions stronger than the thymus atrophy. Moreover, the development of a fibrosis of the pancreas and a cirrhosis of liver several weeks after single administration of DBTC to rats was inhibited by DMPS and DMSA. The antidotal effects on serum parameter were observed after both administration routes of the chelators. DMPS was more effective than DMSA in most measured parameters. The decrease in the biliary excretion of organotin by DMPS and DMSA seems to be the reason for the pronounced protective effects of DMPS and DMSA on bile duct, pancreas and liver. 3. For the treatment of poisonings with dibutyltin compounds, the administration of DMPS or DMSA can be recommended.
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PMID:Antidotal effects of 2,3-dimercaptopropane-1-sulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) on the organotoxicity of dibutyltin dichloride (DBTC) in rats. 1077 44

IFN-inducible protein-10 (IP-10/CXCL10) is a CXC chemokine that targets both T cells and NK cells. Elevation of IP-10 expression has been demonstrated in a number of human diseases, including chronic cirrhosis and biliary atresia. Cytokine-responsive gene-2 (Crg-2), the murine ortholog of IP-10, was induced following CCl(4) treatment of the hepatocyte-like cell line AML-12. Crg-2 expression was noted in vivo in multiple models of hepatic and bile duct injury, including bile duct ligation and CCl(4), D-galactosamine, and methylene dianiline toxic liver injuries. Induction of Crg-2 was also examined following two-thirds hepatectomy, a model that minimally injures the remaining liver, but that requires a large hepatic regenerative response. Crg-2 was induced in a biphasic fashion after two-thirds hepatectomy, preceding each known peak of hepatocyte DNA synthesis. Induction of Crg-2 was also observed in the kidney, gut, thymus, and spleen within 1 h of two-thirds hepatectomy. Characteristic of an immediate early gene, pretreatment of mice with the protein synthesis inhibitor cycloheximide before either two-thirds hepatectomy or CCl(4) injection led to Crg-2 superinduction. rIP-10 was demonstrated to have hepatocyte growth factor-inducing activity in vitro, but alone had no direct mitogenic effect on hepatocytes. Our data demonstrate that induction of Crg-2 occurs in several distinct models of liver injury and regeneration, and suggest a role for CRG-2/IP-10 in these processes.
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PMID:Cytokine-responsive gene-2/IFN-inducible protein-10 expression in multiple models of liver and bile duct injury suggests a role in tissue regeneration. 1141 76

Regeneration and tolerance factor (RTF) is a protein with immunosuppressive activity and is normally present in the thymus and placenta. RTF was measured in the livers of patients with regenerating nodules due to alcoholic cirrhosis and hepatitis C. RTF was expressed in the regenerating nodules of 26 patients with alcoholic cirrhosis. All patients with chronic hepatitis C without cirrhosis failed to express RTF. Flow cytometry revealed upregulation of RTF on the lymphocytes from alcoholic cirrhosis and downregulation in hepatitis C disease.
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PMID:Expression of a novel protein by regenerating hepatocytes and peripheral blood lymphocytes. 1168 81

Di-n-butyltin dichloride (DBTC) induced thymus atrophy, bile duct lesions, pancreatitis, and liver lesions in rats. Depending on dose [6 and 8 mg/kg intravenous (i.v.) DBTC] and time (1-24 weeks), the lesions in pancreas developed to a pancreatic fibrosis and the lesions in liver to liver cirrhosis. A single i.v. administration of 4 mg/kg DBTC induces a mild interstitial pancreatitis after 2-4 days followed by a restitutio ad integrum after 21-28 days. In the present study, the lesions of biliopancreatic duct, pancreas, and liver of rats after repeated administration of 4 mg/kg DBTC i.v. at intervals of 3 weeks have been investigated. The histopathological changes of pancreas and liver were examined by light microscopy 1,4, and 7 days and 2,3,4,6,9, and 12 weeks after administration of DBTC. Furthermore, pathobiochemical parameters of pancreatitis (amylase and lipase activity in serum), liver lesions (alkaline phosphatase activity and bilirubin in serum), and of fibrosis (hyaluronic acid in serum) were studied. Repeated administration of rats with DBTC (4 mg/kg i.v.) at intervals of 3 weeks induced an acute interstitial pancreatitis and after 9-12 weeks, a pancreatic fibrosis and liver lesions (intrahepatic bile duct hyperplasia, inflammation in periportal tract, and necrosis). In serum, elevated levels of alkaline phosphatase, bilirubin, and hyaluronic acid were found. This study demonstrates that the organotin compound induces toxic effects on pancreas and liver of rats by repeated administration of lower doses at long intervals. The risk of exposure to organotin at long intervals should be considered.
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PMID:Repeated administration of a mild acute toxic dose of di-n-butyltin dichloride at intervals of 3 weeks induces severe lesions in pancreas and liver of rats. 1172 88

Triamterene is a potassium-sparing diuretic used in the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and other diseases in which edema may occur. Toxicity and carcinogenicity studies were conducted by administering triamterene (greater than 99% pure) in feed to groups of male and female F344/N rats and B6C3F1 mice for 15 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Chinese hamster ovary cells. 15-day Studies: Groups of five male and five female rats were fed diets containing 0, 1,000, 3,000, 10,000, 30,000, or 60,000 ppm triamterene. The diets containing 10,000 ppm or more were unpalatable, and feed consumption by the 3,000 ppm groups was reduced. Rats exposed to 1,000 or 3,000 ppm triamterene received approximate doses of 80 or 60 mg/kg body weight per day (males) or 70 or 50 mg/kg per day (females). One male rat and two female rats receiving 3,000 ppm died during the second week of the study. The final mean body weights of 3,000 ppm male and female rats were significantly lower than those of controls. Rats in the 3,000 ppm groups had renal tubule regeneration and cytoplasmic vacuolization of the zona glomerulosa of the adrenal gland. Groups of five male and five female mice were fed diets containing 0, 300, 1,000, 3,000, 10,000, or 30,000 ppm triamterene, but the diets containing 10,000 or 30,000 ppm were unpalatable. All mice receiving 3,000 ppm died by day 6. Mice exposed to 300 or 1,000 ppm triamterene received approximate doses of 40 or 155 mg/kg body weight per day (males) or 45 or 170 mg/kg body weight per day (females). The final mean body weights of mice in the 300 and 1,000 ppm groups were similar to those of the controls. Renal tubule degeneration and necrosis were observed in the kidney of 3,000 ppm mice. 13-Week Studies: Groups of 10 male and 10 female rats were fed diets containing 0, 150, 300, 600, 1,200, or 2,400 ppm triamterene. All rats receiving 2,400 ppm died before the end of the study; all other rats survived to the end of the study. Rats exposed to 150, 300, 600, or 1,200 ppm triamterene received approximate doses of 10, 20, 40, or 70 mg/kg body weight per day (males) or 10, 20, 40, or 80 mg/kg per day (females). Body weight gains and final mean body weights of rats in the 1,200 ppm groups were significantly lower than those of controls. There were no biologically significant differences in hematologic, clinical chemistry, or urinalysis parameters among exposed and control rats. Calculi were observed in the renal pelvis of four male rats in the 1,200 ppm group. Chemical-related lesions were observed in the kidney and adrenal gland of rats in the 1,200 and 2,400 ppm groups. These consisted of degeneration and regeneration of the renal tubule epithelium and cytoplasmic vacuolization of cells of the zona glomerulosa of the adrenal cortex. Depletion of hematopoietic cells from the bone marrow and of lymphocytes from the spleen and thymus of rats in the 2,400 ppm groups may have been related to debilitation and reduced feed consumption rather than chemical exposure. Groups of 10 male and 10 female mice were fed diets containing 0, 100, 200, 400, 800, or 1,600 ppm triamterene. All mice receiving 1,600 ppm, one 800 ppm female, one 200 ppm male, and four 100 ppm males died before the end of the study. Mice exposed to 100, 200, 400, or 800 ppm triamterene received approximate doses of 15, 25, 50, or 90 mg/kg body weight per day (males) or 15, 25, 50, or 115 mg/kg per day (females). The body weight gain and final mean body weight of male mice receiving 800 ppm were significantly lower than those of the controls. The total leukocyte and lymphocyte counts of males receiving 800 ppm and of females receiving 100, 400, or 800 ppm were significantly lower than those of controls. No other differences in hematologic, clinical chemistry, or urinalysis parameters were considered to be biologically significant. Necrosis of Lymphocytes was observed in the lymph node, spleen, and thymus of mice in the 800 and 1,600 ppm groups groups. 2-Year Studies: The doses selected for the 2-year studies were based on lower body weights, mortality, and chemical-related lesions observed in exposed animals during the 13-week studies. Groups of 70 male and 70 female rats were fed diets containing 0, 150, 300, or 600 ppm triamterene and groups of 70 male and 70 female mice were fed diets containing 0, 100, 200, or 400 ppm. Ten animals from each group were included for interim evaluations at 3 and 15 months. Because of a dosing error involving the high-dose mice at week 40, a second study was conducted with groups of 60 male and 60 female mice fed diets containing 0 or 400 ppm triamterene. In the 2-year studies, rats exposed to 150, 300, or 600 ppm triamterene received approximately 5,10, or 25 mg/kg body weight per day (males) and 5, 15, or 30 mg/kg (females) and mice exposed to 100, 200, or 400 ppm received approximately 10, 25, or 45 mg/kg (males) and 15, 30, or 60 mg/kg (females) per day. 3-Month and 15-Month Interim Evaluations in the 2-Year Studies: There were no biologically significant differences in hematologic, clinical chemistry, or urinalysis parameters between exposed and control rats or mice at the 3- or 15-month interim evaluations. At necropsy, the mean body weights of exposed rats and mice were similar to those of the controls. There were no chemical-related lesions in exposed rats at 3 months or in exposed mice at 3 or 15 months. At the 15-month evaluation, basophilic, clear cell, and mixed cell foci of the liver occurred in exposed male rats. No chemical-related lesions were observed in female rats at 15 months. Survival, Body Weights, Clinical Findings, and Feed Consumption in the 2-Year Studies: Survival of exposed rats was similar to that of controls (males: 0 ppm, 25/47; 150 ppm, 25/50; 300 ppm, 19/50; 600 ppm, 27/50; females: 29/50, 34/50, 34/50, 29/50). The mean body weights of 600 ppm rats were consistently lower than, but within 5&percnt; of, those of controls after week 49. Feed consumption by male and female rats was similar among exposed and control groups throughout the studies. There were no clinical findings of toxicity. Survival of 400 ppm male mice in the first study was lower than that of controls because of the dosing accident at week 40. Survival of 100 and 200 ppm male mice and of all exposed groups of female mice in the first study and of exposed males and females in the second study was similar to controls (males: first study, 0 ppm, 47/50; 100 ppm, 45/50; 200 ppm, 46/50; 400 ppm, 46/60; second study, 0 ppm, 43/50; 400 ppm, 39/50; females: first study, 38/50; 43/50; 43/50; 43/60; second study, 40/50; 38/51). Mean body weights of exposed mice were similar to those of controls throughout the first study with one exception; in the week following the dosing error, the mean body weight of 400 ppm males was 16&percnt; lower than that of controls. In the second study, mean body weights of 400 ppm mice were slightly lower than those of controls during the final 8 weeks. Feed consumption by exposed mice was similar to that by controls throughout the studies. There were no clinical findings of toxicity in exposed mice. Neoplasms and Nonneoplastic Lesions in the 2-Year Studies: The incidences of mixed cell foci and focal hyperplasia of the liver were significantly increased in 300 and 600 ppm male rats, and the incidences of clear cell and mixed cell foci were significantly increased in 300 and 600 ppm female rats. Hepatocellular adenomas occurred in all groups of exposed male rats, but none occurred in controls; the incidence of hepatocellular adenoma in the 150 ppm males was significantly higher than that of controls (O ppm, 0/50; 150 ppm, 6/50; 300 ppm, 4/50; 600 ppm, 3/49). Hepatocellular adenomas were observed in two 600 ppm female rats, but not in the lower exposure groups or in controls. No hepatocellular carcinomas were seen in exposed or control rats. The incidences of nephropathy in exposed rats were similar to those of controls, but the average severity of the lesion was marginally increased in male rats receiving 300 ppm and in female rats receiving 600 ppm (males: 47/50, 2.4; 49/50, 2.7; 50/50, 3.0; 49/50, 2.8; females: 38/50, 1.1; 45/50, 1.2; 45/50, 1.3; 45/50, 1.4). Although in the first study the incidences of hepatocellular adenoma in exposed male mice were similar to that of controls, the incidences of multiple adenomas were greater in the exposed groups, and the incidence of hepatocellular carcinoma in the 400 ppm group was marginally greater (hepatocellular adenoma: 0 ppm, 17/50; 100 ppm, 22/50; 200 ppm, 19/50; 400 ppm, 20/60; hepatocellular carcinoma: 5/50; 7/50; 3/50; 13/60). In the second study, the incidence of hepatocellular adenoma in the 400 ppm males was significantly higher than that of controls (hepatocellular adenoma: 0 ppm, 21/50; 400 ppm, 36/50; hepatocellular carcinoma: 9/50; 11/50). The incidences of hepatocellular adenoma in exposed female mice in the first and second studies were significantly greater than those of controls (hepatocellular adenoma, first study: 10/50; 22/50; 23/50; 36/60; second study: 7/50; 28/51). The incidences of multiple adenoma were also increased in the exposed groups. Although the incidences of hepatocellular carcinoma were similar among exposed and control female mice in the first study, the incidence of hepatocellular carcinoma in the 400 ppm females in the second study was marginally greater than that of controls (hepatocellular carcinoma, first study: 4/50; 4/50; 3/50; 8/60; second study: 5/50; 11/50). In both studies, hepatocellular foci (basophilic, eosinophilic, clear cell, or mixed cell) also occurred more frequently in exposed female mice than in controls. The incidences of thyroid gland follicular cell hyperplasia in the 200 and 400 ppm males and in all exposed groups of females were significantly greater than those of controls in the first study. These findings were confirmed in the second study (follicular cell hyperplasia: males, first study, 3/50, 8/50, 16/50, 20/60; second study, 0/50,16/50; females, first study, 4/49,17/49,18/50, 28/60; second study, 9/50, 32/51). The incidences of follicular cell neoplasms were similar among exposed and control mice in both studies. The incidences (28/50, 36/50, 43/50, 49/60) and average severity (0.56, 0.80, 1.00, 1.07) of nephropathy were marginally higher in exposed female mice than in controls in the first study. In the second study, the differences in incidence (15/50, 21/50) and severity (0.38, 0.55) were not as great. It is uncertain if these increases were related to the ingestion of triamterene. The incidences and severity of nephropathy were similar among exposed and control male mice in both studies. Genetic Toxicology: Triamterene was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 with or without exogenous metabolic activation (S9). It did not induce chromosomal aberrations in Chinese hamster ovary cells, with or without S9. Positive results were obtained for induction of sister chromatid exchanges in Chinese hamster ovary cells with and without S9. Conclusions: Under the conditions of these 2-year feed studies, there was equivocal evidence of carcinogenic activity of triamterene in male F344/N rats based on a marginal increase in the incidence of hepatocellular adenoma. There was no evidence of carcinogenic activity of triamterene in female F344/N rats administered 150, 300, or 600 ppm. There was some evidence of carcinogenic activity of triamterene in male B6C3F1 mice based on a marginal increase in the incidence of hepatocellular carcinoma in the first study and a significantly increased incidence of hepatocellular adenoma in the second study. There was some evidence of carcinogenic activity of triamterene in female B6C3F1 mice based on significantly increased incidences of hepatocellular adenoma and of adenoma and carcinoma (combined). Exposure to triamterene was associated with an increased incidence of hepatocellular foci, primarily mixed cell type, and an increase in the severity of nephropathy in female rats. In mice, exposure to triamterene was associated with an increased incidence of hepatocellular foci in females and an increased incidence of thyroid gland follicular cell hyperplasia in males and females. Synonyms: 6-Phenyl-2,4,7-pteridinetnamine; 6-phenyl-2,4,7-triaminopteridine; 2,4,7-triamino-6-phenypteridine; ademin; pterofen; pterophane; NSC-77625; SKF 8542 Trade names: Dyrenium, Dyazide, Dyren, Dytac, Jatropur, Maxzide, Noridyl, Triteren, Teriam, Urocaudal
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PMID:NTP Toxicology and Carcinogenesis Studies of Triamterene (CAS No. 396-01-0) in F344/N Rats and B6C3F1 Mice (Feed Studies). 1261 91

A post-mortem examination, in the case of a 34-year-old man dying suddenly from head injuries sustained in a road accident, showed early cirrhosis of the liver and associated splenomegaly 17 years after an attack of infective hepatitis. The histology of the thymus showed abnormal changes in the medulla, consisting of epithelial hyperplasia and the presence of lymph follicles with germinal centres. It is suggested that an auto-immune mechanism underlay the pathogenesis of the cirrhosis and that the thymic changes were concerned with this.
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PMID:THE THYMUS IN HEPATIC CIRRHOSIS. 1406 30

Chronic hepatitis B virus infection is a serious problem because of its worldwide distribution and possible adverse chronic sequelae, such as cirrhosis and hepatocellular carcinoma. Chronic hepatitis B infection is a dynamic state of interactions between the virus, hepatocyte and host immune response. Interferon-alpha and direct antiviral agents, such as lamivudine (Epivir, GlaxoSmithKline), are effective in the therapy of chronic HBV infection but the efficacy is far from satisfactory. Thymalfasin (thymosin alpha1; Talpha1, Zadaxintrade mark, SciClone Pharmaceuticals, Inc.) is a 28-amino acid polypeptide produced synthetically but originally isolated from thymosin fraction 5, a bovine thymus extract containing a number of immunologically active peptides. In vitro studies have shown that Talpha1 can influence T-cell production and maturation, stimulate production of Th1 cytokines such as interferon-gamma and interleukin-2, and activate natural killer cell-mediated cytotoxicity. Seven randomized controlled studies on Talpha1 monotherapy in patients with chronic hepatitis B showed that 6 months treatment with Talpha1 (1.6 mg twice-weekly) resulted in a significantly higher sustained response rate than untreated controls. The benefits of Talpha1 therapy is usually not immediately apparent during therapy. There is a trend for complete virological response to increase or accumulate gradually after the end of thymosin therapy. The results of Talpha1 and interferon combination therapy in two open-label trials were also promising. In terms of the mechanisms of action, a combination of Talpha1 and nucleoside or nucleotide analogs is a logical approach in the control of chronic HBV infection and a randomized control study is ongoing.
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PMID:Thymalfasin for the treatment of chronic hepatitis B. 1548 67

Urotensin II (U-II) is the most potent vasoconstrictor known, even more potent than endothelin-1. It was first isolated from the fish spinal cord and has been recognized as a hormone in the neurosecretory system of teleost fish for over 30 years. After the identification of U-II in humans and the orphan human G-protein-coupled receptor 14 as the urotensin II receptor, UT, many studies have shown that U-II may play an important role in cardiovascular regulation. Human urotensin II (hU-II) is an 11 amino acid cyclic peptide, generated by proteolytic cleavage from a precursor prohormone. It is expressed in the central nervous system as well as other tissues, such as kidney, spleen, small intestine, thymus, prostate, pituitary, and adrenal gland and circulates in human plasma. The plasma U-II level is elevated in renal failure, congestive heart failure, diabetes mellitus, systemic hypertension and portal hypertension caused by liver cirrhosis. The effect of U-II on the vascular system is variable, depending on species, vascular bed and calibre of the vessel. The net effect on vascular tone is a balance between endothelium-independent vasoconstriction and endothelium-dependent vasodilatation. U-II is also a neuropeptide and may play a role in tumour development. The development of UT receptor antagonists may provide a useful research tool as well as a novel treatment for cardiorenal diseases.
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PMID:Urotensin II: its function in health and its role in disease. 1588 58

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